Dr Gergely Toth MBA

Gergely Toth, EMBA

University position

Investigator; WT/MRC Neurodegen. Initiative, NIHR BRU Dementia

Dr Gergely Toth MBA is pleased to consider applications from prospective PhD students.

Departments

Department of Clinical Neurosciences

Institutes

Wolfson Brain Imaging Centre

Home page

http://www.wbic.cam.ac.uk/

Research Theme

Cellular and Molecular Neuroscience

Interests

My research interests include the targeting of intrinsically disordered proteins by small molecules, which misfold and lose their native functions and/or gain toxic functions implicated in neurodegenerative diseases. We are working on multidisciplinary drug discovery programs to target tau and Abeta peptide for Alzheimer’s disease, and alpha-synuclein for Parkinson’s disease by applying, in synergy, structure based computer aided modeling approaches, biophysical screening methods, NMR and relevant cellular and in vivo models of these diseases. Our goal is to identify and characterize such protein-small molecule systems in detail and to develop these hits into leads with in vivo efficacy in AD and PD disease models.

Schematic representation of our approach to therapeutic targeting of intrinsically disordered proteins by small molecules
View image full-size (1500x637 pixels)

Research Focus

Keywords

computer aided drug desing

structure based drug design

protein misfolding and aggregation

small molecule chaperone

biophysics and structure biology of protein-ligand interactions

Clinical conditions

Alzheimer's disease

Dementia

Parkinson's disease

Equipment

biophysical methods

Computational modelling

in vitro assays

structure based drug design

Collaborators

Cambridge

Franklin Aigbirhio

Christopher Dobson

Peter St. George-Hyslop

International

Yun Kee Web: http://si.kangwon.ac.kr/content...

Byung-Soo Koo Web: http://web.dongguk.ac.kr/english...

Eckhard Mandelkow Web: http://www.dzne.de/en/cent...

Lisa McConlouge

Thomas Neumann Web: http://www.graffinity.com/

Associated News Items


    Key publications

    Tóth G, Gardai SJ, Zago W, Bertoncini CW, Cremades N, Roy SL, Tambe MA, Rochet JC, Galvagnion C, Skibinski G, Finkbeiner S, Bova M, Regnstrom K, Chiou SS, Johnston J, Callaway K, Anderson JP, Jobling MF, Buell AK, Yednock TA, Knowles TP, Vendruscolo M, Christodoulou J, Dobson CM, Schenk D, McConlogue L (2014), “Targeting the intrinsically disordered structural ensemble of α-synuclein by small molecules as a potential therapeutic strategy for Parkinson's disease.” PLoS One 9(2):e87133 Details

    Toth G (2013), “The financial ecosystem available to early-stage biotechnology firms and its misalignment with interests of these firms, of the biotechnology industry and with global disease burden” Journal of Commercial Biotechnology 19: 16-27

    Tóth G, Moitessier N (2013), “EDITORIAL: Advances in Computational Structure Based Drug Discovery.” Curr Pharm Des Details

    Zhu M, De Simone A, Schenk D, Toth G, Dobson CM, Vendruscolo M (2013), “Identification of small-molecule binding pockets in the soluble monomeric form of the Aβ42 peptide.” J Chem Phys 139(3):035101 Details

    Buell AK, Esbjörner EK, Riss PJ, White DA, Aigbirhio FI, Toth G, Welland ME, Dobson CM, Knowles TP (2011), “Probing small molecule binding to amyloid fibrils.” Phys Chem Chem Phys 13(45):20044-52 Details

    Truong AP, Tóth G, Probst GD, Sealy JM, Bowers S, Wone DW, Dressen D, Hom RK, Konradi AW, Sham HL, Wu J, Peterson BT, Ruslim L, Bova MP, Kholodenko D, Motter RN, Bard F, Santiago P, Ni H, Chian D, Soriano F, Cole T, Brigham EF, Wong K, Zmolek W, Goldbach E, Samant B, Chen L, Zhang H, Nakamura DF, Quinn KP, Yednock TA, Sauer JM (2010), “Design of an orally efficacious hydroxyethylamine (HEA) BACE-1 inhibitor in a preclinical animal model.” Bioorg Med Chem Lett 20(21):6231-6 Details

    Lendel C, Bertoncini CW, Cremades N, Waudby CA, Vendruscolo M, Dobson CM, Schenk D, Christodoulou J, Toth G (2009), “On the mechanism of nonspecific inhibitors of protein aggregation: dissecting the interactions of alpha-synuclein with Congo red and lacmoid.” Biochemistry 48(35):8322-34 Details

    Tóth G, Bowers SG, Truong AP, Probst G (2007), “The role and significance of unconventional hydrogen bonds in small molecule recognition by biological receptors of pharmaceutical relevance.” Curr Pharm Des 13(34):3476-93 Details

    Tóth G, Mukhyala K, Wells JA (2007), “Computational approach to site-directed ligand discovery.” Proteins 68(2):551-60 Details

    Tóth G, Borics A (2006), “Closing of the flaps of HIV-1 protease induced by substrate binding: a model of a flap closing mechanism in retroviral aspartic proteases.” Biochemistry 45(21):6606-14 Details

    Carnevali P, Tóth G, Toubassi G, Meshkat SN (2003), “Fast protein structure prediction using Monte Carlo simulations with modal moves.” J Am Chem Soc 125(47):14244-5 Details

    Tóth G, Murphy RF, Lovas S (2001), “Investigation of aromatic-backbone amide interactions in the model peptide acetyl-Phe-Gly-Gly-N-methyl amide using molecular dynamics simulations and protein database search.” J Am Chem Soc 123(47):11782-90 Details

    Tóth G, Watts CR, Murphy RF, Lovas S (2001), “Significance of aromatic-backbone amide interactions in protein structure.” Proteins 43(4):373-81 Details